The steps by which E. coli strains harboring mutations related to fosfomycin resistance arise and spread during urinary tract infections (UTIs) are far from being understood. A study performed by several REIPI groups (Hospital Universitario Virgen del Rocío, Hospital Universitario Virgen Macarena and Centro Nacional de Biotecnología) evaluates the effects of the urinary tract conditions (urine, pH, and anaerobiosis) on fosfomycin activity against a set of isogenic strains carrying the most prevalent chromosomal mutations conferring fosfomycin resistance (ΔuhpT, ΔglpT, ΔcyaA, and ΔptsI), either singly or in combination, and some fosfomycin-resistant E. coli clinical isolates from patients with UTI. The results have revealed that Urinary tract physiological conditions have a profound impact on fosfomycin activity against strains with chromosomal fosfomycin resistance mutations. Specifically, acidic pH values and anaerobiosis convert most of the strains categorized as resistant to fosfomycin according to the international guidelines to a susceptible status. Therefore, urinary pH values may have practical interest in the management of UTIs. Finally, our results, together with the high fitness cost associated with fosfomycin resistance mutations, might explain the low prevalence of fosfomycin-resistant E. coli variants in UTIs.
The study has been published in Antimicrobial Agents and Chemotherapy. Martín-Gutiérrez G, Docobo-Pérez F, Rodriguez-Beltrán J, Rodríguez-Martínez JM, Aznar J, Pascual A, Blázquez J. 2018. Urinary tract conditions affect fosfomycin activity against Escherichia coli strains harboring chromosomal mutations involved in fosfomycin uptake. Antimicrob Agents Chemother 62:e01899-17. https://doi.org/10 .1128/AAC.01899-17